Device and methods comprising microelectrode arrays for electroconductive cells

Abstract

The present invention relates to the devices and method comprising microelectrode arrays for the differentiation, maturation and functional analysis of electroconductive cells, including muscle cells (including, but not limited to, cardiomyocytes, skeletal muscle myocytes and smooth muscle myocytes) and neuronal cells. The microelectrode present on the arrays can be used to stimulate and record from cells cultured on the substrate. In some embodiments, the substrate has a substantially smooth surface, and in other embodiments the substrate is nanotextured, including an array of substantially parallel grooves and ridges of nanometer-micrometer widths.

1 . A substrate comprising a plurality of microelectrodes and electroconductive cells, wherein the microelectrodes contact the electroconductive cells, and wherein the microelectrodes are connected to an electronic interface to transmit a signal input to the cells or record the electrical signals from the cells. 
     
     
         2 .- 15 . (canceled) 
     
     
         16 . The substrate of  claim 1 , wherein the electroconductive cells are muscle cells. 
     
     
         17 . The substrate of  claim 1 , wherein the muscle cells are selected from cardiomyocytes, skeletal muscle myocytes, and smooth muscle myocytes. 
     
     
         18 . The substrate of  claim 1 , wherein the electroconductive cells are neuronal cells. 
     
     
         19 . The substrate of  claim 1 , wherein the substrate has a substantially smooth surface. 
     
     
         20 . The substrate of  claim 1 , wherein the substrate has a nanotextured surface. 
     
     
         21 . The substrate of  claim 20 , wherein the nanotextured surface comprises a substantially parallel array of grooves and ridges. 
     
     
         22 . The substrate of  claim 21 , wherein the depth of the grooves is between 10 nm-10 μm, the width of the grooves is between 50 nm-10 μm, and the ridges between the grooves have a width of between 50 nm-10 μm. 
     
     
         23 . The substrate of  claim 22 , wherein the depth of the grooves is between 50 nm-500 nm, the width of the grooves is between 200 nm-1000 nm, and the ridges between the grooves have a width of between 200 nm-1000 nm. 
     
     
         24 . A method for disease modeling comprising using the substrate of  claim 1  in which the cells are derived from a subject with a muscular disease or disorder. 
     
     
         25 . An assay for assessing the effect of an agent on at least one biopotential or electrical property of a population of electroconductive cells, the assay comprising culturing the population of electroconductive cells on the substrate of  claim 1 , contacting the electroconductive cells with at least one agent, and measuring at least one of: the growth; viability; and a biopotential or electrical property of the population of electroconductive cells. 
     
     
         26 . The assay of  claim 25 , wherein the effect is a toxic or aberrant effect on at least one of the biopotentials or electrical properties of the electroconductive cells. 
     
     
         27 . The assay of  claim 25 , wherein the at least one biopotential of the electroconductive cells is measured on the surface of the microelectrode array. 
     
     
         28 . A system comprising:
 (a) a substrate comprising microelectrodes, wherein the microelectrodes on the substrate are connected to an electronic interface,   (b) an electronic interface which is connected to a computer   (c) a computer, wherein the computer instructs the electronic interface for the transmission of electric signals to and from the microelectrodes on the substrate.   
     
     
         29 . The system of claim  14 , wherein the substrate comprising microelectrodes comprises electroconductive cells. 
     
     
         30 . The substrate of  claim 1 , wherein the electroconductive cells are arranged in an anisotropic and polarized cell arrangement. 
     
     
         31 . The substrate of  claim 1 , further comprising a shielding layer below the microelectrodes, where the shielding layer comprises a thin film metal and an insulating layer. 
     
     
         32 . The assay of claim  11 , wherein the electroconductive cells are selected from the group consisting of: neuronal cells; cardiomyocytes; skeletal muscle myocytes; smooth muscle myocytes; or a combination thereof. 
     
     
         33 . The assay of claim  11 , wherein the electroconductive cells are obtained from, or descended from cells of a healthy human subject, or a human subject with a cardiac disease. 
     
     
         34 . The assay of claim  11 , wherein at least one electrical property of the electroconductive cell is electrical impedance.